Since first identified in mammalian mRNA in the 1970s, N6-methyladenosine (m6A) has been proposed to regulate mRNA processing including alternative splicing, RNA degradation and translation. In both mammals and yeast, m6A methylation of RNA preferentially occurs within the consensus sequence RRACH (R=G or A; H=A, C or U) in gene coding regions and 3’UTRs, implicating fundamental roles in RNA processing and translational control.

The recent identification and characterization of the m6A methyltransferase WMM complex (WTAP-METTL3-METTL14), the demethylases FTO and ALKBH5, and YTH-domain containing binding proteins highlighted the biological significance of m6A methylation. However，the role of m6A in mRNA processing remains largely unknown.

The lab of Prof. YANG Yungui from Beijing Institute of Genomics, Chinese Academy of Sciences (CAS), revealed that FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. The work has been published online in Cell Research.

These findings provide compelling evidence that FTO-dependent m6A methylation may function as a novel cis-regulatory element of RNA processing and play a critical role in the regulation of adipogenesis.

This research is supported by CAS, Ministry of Science and Technology and Natural Science Foundation of China.

Cooperative role of m6A in regulating SRSF2 protein at spliced exons (Image by YANG Yungui's lab).